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A phosphodiesterase 4 inhibitor inhibits matrix protein deposition in airways in vitro.
J Allergy Clin Immunol 2006; 118(3):649-57JA

Abstract

BACKGROUND

Airway smooth muscle (ASM) cells may contribute to airway remodeling through the release of growth factors, cytokines, and extracellular matrix (ECM) proteins. The effect of current asthma therapies on this release is not known.

OBJECTIVE

We examined the effect of corticosteroids, long-acting beta(2)-agonists, and a phosphodiesterase 4 (PDE4) inhibitor on ASM-released connective tissue growth factor (CTGF), collagen I, fibronectin, versican, and IL-6.

METHODS

Airway smooth muscle cells from individuals with and without asthma were stimulated with TGF-beta with or without the drugs and CTGF and ECM protein expression measured by real-time PCR, cell surface, or matrix-associated ELISA. IL-6 release was measured by ELISA. Bronchial rings from individuals without asthma were incubated with TGF-beta with or without the drugs.

RESULTS

Neither corticosteroids nor long-acting beta(2)-agonists reduced TGF-beta-induced CTGF, collagen I, or fibronectin in either cell type, whereas corticosteroids alone induced the expression of CTGF, collagen I, and fibronectin. These drugs did not prevent the accumulation of TGF-beta-induced proteins in bronchial rings, whereas the PDE4 inhibitor roflumilast inhibited TGF-beta-induced CTGF, collagen I, and fibronectin.

CONCLUSION

In our model, current asthma therapies are not able to inhibit matrix protein deposition from ASM cells. The results of this study suggest that the PDE4 inhibitor roflumilast may have a role in regulating the ECM and therefore aspects of airway remodeling in asthma.

CLINICAL IMPLICATIONS

Although current asthma therapies are effective in reducing inflammation and symptoms, reversal or prevention of structural changes contributing to remodeling may require additional therapy, which could include PDE4 inhibitors.

Authors+Show Affiliations

Department of Pharmacology, University of Sydney, NSW, Australia. janette@pharmacol.usyd.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16950284

Citation

Burgess, Janette K., et al. "A Phosphodiesterase 4 Inhibitor Inhibits Matrix Protein Deposition in Airways in Vitro." The Journal of Allergy and Clinical Immunology, vol. 118, no. 3, 2006, pp. 649-57.
Burgess JK, Oliver BG, Poniris MH, et al. A phosphodiesterase 4 inhibitor inhibits matrix protein deposition in airways in vitro. J Allergy Clin Immunol. 2006;118(3):649-57.
Burgess, J. K., Oliver, B. G., Poniris, M. H., Ge, Q., Boustany, S., Cox, N., ... Black, J. L. (2006). A phosphodiesterase 4 inhibitor inhibits matrix protein deposition in airways in vitro. The Journal of Allergy and Clinical Immunology, 118(3), pp. 649-57.
Burgess JK, et al. A Phosphodiesterase 4 Inhibitor Inhibits Matrix Protein Deposition in Airways in Vitro. J Allergy Clin Immunol. 2006;118(3):649-57. PubMed PMID: 16950284.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A phosphodiesterase 4 inhibitor inhibits matrix protein deposition in airways in vitro. AU - Burgess,Janette K, AU - Oliver,Brian G G, AU - Poniris,Maree H, AU - Ge,Qi, AU - Boustany,Sarah, AU - Cox,Natalie, AU - Moir,Lyn M, AU - Johnson,Peter R A, AU - Black,Judith L, Y1 - 2006/07/20/ PY - 2005/12/12/received PY - 2006/05/17/revised PY - 2006/05/19/accepted PY - 2006/9/5/pubmed PY - 2006/10/18/medline PY - 2006/9/5/entrez SP - 649 EP - 57 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 118 IS - 3 N2 - BACKGROUND: Airway smooth muscle (ASM) cells may contribute to airway remodeling through the release of growth factors, cytokines, and extracellular matrix (ECM) proteins. The effect of current asthma therapies on this release is not known. OBJECTIVE: We examined the effect of corticosteroids, long-acting beta(2)-agonists, and a phosphodiesterase 4 (PDE4) inhibitor on ASM-released connective tissue growth factor (CTGF), collagen I, fibronectin, versican, and IL-6. METHODS: Airway smooth muscle cells from individuals with and without asthma were stimulated with TGF-beta with or without the drugs and CTGF and ECM protein expression measured by real-time PCR, cell surface, or matrix-associated ELISA. IL-6 release was measured by ELISA. Bronchial rings from individuals without asthma were incubated with TGF-beta with or without the drugs. RESULTS: Neither corticosteroids nor long-acting beta(2)-agonists reduced TGF-beta-induced CTGF, collagen I, or fibronectin in either cell type, whereas corticosteroids alone induced the expression of CTGF, collagen I, and fibronectin. These drugs did not prevent the accumulation of TGF-beta-induced proteins in bronchial rings, whereas the PDE4 inhibitor roflumilast inhibited TGF-beta-induced CTGF, collagen I, and fibronectin. CONCLUSION: In our model, current asthma therapies are not able to inhibit matrix protein deposition from ASM cells. The results of this study suggest that the PDE4 inhibitor roflumilast may have a role in regulating the ECM and therefore aspects of airway remodeling in asthma. CLINICAL IMPLICATIONS: Although current asthma therapies are effective in reducing inflammation and symptoms, reversal or prevention of structural changes contributing to remodeling may require additional therapy, which could include PDE4 inhibitors. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/16950284/A_phosphodiesterase_4_inhibitor_inhibits_matrix_protein_deposition_in_airways_in_vitro_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(06)01194-8 DB - PRIME DP - Unbound Medicine ER -